UNMC researcher publishes perspective on new CRSPR technology

UNMC researcher Channabasavaiah Gurumurthy, PhD, and his collaborator Masato Ohtsuka, PhD, from Tokai University, Japan, recently published a perspective piece in Nature Protocols that lays out a plan to use CRSPR technology to build upon a newly discovered mRNA delivery system, selective endogenous encapsidation for cellular delivery (SEND).

The only paper on SEND thus far was published a year ago in Science by one of the pioneers of CRISPR technology. The paper demonstrated that mRNAs can be packaged in virus-like particles to transport them from one cell to another. A protein, called PEG10, fundamentally important for development in both humans and animals, was discovered as a key molecule that orchestrates forming virus like particles coating mRNA cargoes.  

But as yet, the delivery system has not been shown to work in animals. In the Nature Protocols perspective paper, the authors propose ideas and genetically engineered animal models useful for researching SEND.

To prove that the SEND delivery system works in animal models is the challenge, Dr. Gurumurthy said.

“The mRNA has to be assembled, the protein has to be assembled, the parts of the envelope have to be assembled, to demonstrate that the SEND phenomenon works in animals,” he said.

The stakes could be high: Dr. Gurumurthy’s paper suggests that the delivery system, once developed, could be used as a tool for “intra-uterine gene therapy for diseases such as lysosomal storage disorders, hemoglobinopathies, spinal muscular atrophy, Down syndrome and cystic fibrosis.”

The authors already have made progress in testing some of their hypotheses in the perspective paper and has another paper out for review currently. Dr. Gurumurthy continues to seek NIH funding for a proposed “high-risk, high-reward” proposal.

“If this SEND process is proven effective in live organism, it can be used as a gene therapy tool, perhaps as soon as five to 10 years from now,” he said. “We are not there yet, but we need to understand how PEG10 works, how the other components of the virus-like particles work, how the mRNA can be packaged in those particles.

“There are many things to be uncovered, but this has exciting potential as a gene therapy tool.”